Muscarinic receptor antagonists for overactive bladder

Abstract

From time to time we publish a full review of drugs that are available for the treatment of common conditions. In this issue, the review is written by two of the leading authorities in the world, Paul Abrams and Karl‐Erik Andersson, on the topic of overactive bladder and antimuscarinic agents. This in‐depth review covers the entire range of questions that might be asked about this common area of interest. Overactive bladder (OAB) is a syndrome characterized by urinary urgency, with or without urgency urinary incontinence, usually with frequency and nocturia. OAB symptoms are often associated with detrusor overactivity (DO). Like OAB symptoms, the prevalence of DO increases with age and can have a neurogenic and/or myogenic aetiology. Bladder outlet obstruction can be a contributing factor in DO, possibly through cholinergic denervation of the detrusor and supersensitivity of muscarinic receptors to acetylcholine, although the prevalence of OAB is similar in men and women across age groups. Acetylcholine is the primary contractile neurotransmitter in the human detrusor, and antimuscarinics exert their effects on OAB/DO by inhibiting the binding of acetylcholine at muscarinic receptors M2 and M3 on detrusor smooth muscle cells and other structures within the bladder wall. Worldwide, there are six antimuscarinic drugs currently marketed for the treatment of OAB: oxybutynin, tolterodine, propiverine, trospium, darifenacin, and solifenacin. Each has demonstrated efficacy for the treatment of OAB symptoms, but their pharmacokinetic and adverse event profiles differ somewhat due to structural differences (tertiary vs quaternary amines), muscarinic receptor subtype selectivities, and organ selectivities. Antimuscarinics are generally well tolerated, even in special populations (e.g. men with bladder outlet obstruction, elderly patients, children). The most frequently reported adverse events in clinical studies of antimuscarinics are dry mouth, constipation, headache, and blurred vision; few patients withdraw from clinical trials because of adverse events. Development of an antimuscarinic with functional selectivity for the bladder would reduce the occurrence of antimuscarinic adverse events. The therapeutic potential of several other agents, such as α3‐adrenoceptor agonists, purinergic receptor antagonists, phosphodiesterase inhibitors, neurokinin‐1 receptor antagonists, opioids, and Rho‐kinase inhibitors, is also under investigation for the treatment of OAB.

Urodynamics in a community-dwelling population of females 80 years or older: which motive? Which diagnosis?

“…Hashim and Abrams (16) have found that 44% of women with urgency had DO; in our study 54% of the women who complained of urgency had DO, which is slightly higher. This finding could be related to the decline in central nervous system cholinergic activity occurring with normal aging (17). In addition, we observed a high prevalence of DHIC (low detrusor pressure and high residual volume -35%).…”

Novel insights into renal d-amino acid oxidase accumulation: propiverine changes DAAO localization and peroxisomal size in vivo

“…In Europe and the USA, about 15 % of adults suffer from overactive bladder (OAB) (Abrams and Andersson 2007). The International Continence Society defines symptoms of overactive bladder with urgency, urinary frequency, nocturia and urge incontinence (Wein 2011).…”

Treatment for chronic ischaemia-induced bladder detrusor dysfunction using bone marrow mesenchymal stem cells: An experimental study

“…The mechanism of ischaemia-induced bladder dysfunction is complicated, which may be related to ischaemic denervation. This causes M-cholinergic receptor hypersensitivity to acetylcholine (18) and results in detrusor overactivity which leads to more ischaemia in the bladder wall. The current study attempted to implant stem cells into the bladder wall as means to improve the pathological changes caused by ischaemia and improve the function of ischaemic bladder.…”